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杨梅素通过β-连环蛋白通路的下游信号抑制人乳腺癌 MCF-7 细胞中的 p21 激活激酶 1。

Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway.

机构信息

Department of Breast and Thyroid Hernia Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.

Department of Pathology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.

出版信息

Oncol Rep. 2016 Jul;36(1):342-8. doi: 10.3892/or.2016.4777. Epub 2016 Apr 28.

DOI:10.3892/or.2016.4777
PMID:27122002
Abstract

As a main active compound in the bark of waxberry (Myrica rubra), myricetin is a macrocyclic diarylheptanoid, and can trigger the apoptosis of HeLa and PC3 cells. The aim of the present study was to elucidate the anticancer effect of myricetin on human breast cancer MCF-7 cells and to explore the possible mechanisms of action. MCF-7 cells were treated with different concentrations of myricetin (0-80 µM) for 12, 24 and 48 h. In the present study, we found that myricetin suppressed the cell viability of the MCF-7 cells at least partly through the induction of apoptosis as determined by MTT assay and flow cytometry. Western blot analysis revealed that myricetin effectively suppressed the protein expression of p21-activated kinase 1 (PAK1), MEK and phosphorylated extracellular mitogen-activated protein kinase (ERK1/2). In addition, treatment of myricetin activated glycogen synthase kinase-3β (GSK3β) and Bax protein expression, and inhibited β-catenin/cyclin D1/proliferating cell nuclear antigen (PCNA)/survivin and promoted caspase-3 activity in the MCF-7 cells. These results demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells through PAK1/MEK/ERK/GSK3β/β-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling.

摘要

作为杨梅树皮中的一种主要活性化合物,杨梅素是一种大环二芳基庚烷类化合物,可诱导 HeLa 和 PC3 细胞凋亡。本研究旨在阐明杨梅素对人乳腺癌 MCF-7 细胞的抗癌作用,并探讨其可能的作用机制。用不同浓度的杨梅素(0-80μM)处理 MCF-7 细胞 12、24 和 48h。本研究发现,杨梅素通过 MTT 检测和流式细胞术测定,至少部分通过诱导细胞凋亡来抑制 MCF-7 细胞的细胞活力。Western blot 分析显示,杨梅素能有效抑制 PAK1、MEK 和磷酸化细胞外有丝分裂原活化蛋白激酶(ERK1/2)的蛋白表达。此外,杨梅素处理激活糖原合酶激酶-3β(GSK3β)和 Bax 蛋白表达,抑制 β-连环蛋白/周期蛋白 D1/增殖细胞核抗原(PCNA)/生存素,并促进 MCF-7 细胞中 caspase-3 的活性。这些结果表明,杨梅素通过 PAK1/MEK/ERK/GSK3β/β-连环蛋白/周期蛋白 D1/PCNA/生存素/Bax-caspase-3 信号通路抑制人乳腺癌 MCF-7 细胞的细胞活力。

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